ABSTRACT
The combination of malonic and methylmalonic aciduria was first described by A. R. Gregg and colleagues in a child who had seizures and failure to thrive, along with immunodeficiency. Organic acidemia phenotype of recurrent episodes of ketoacidosis; hypoglycemia seizures; failure to thrive; developmental delay; methylmalonic acidemia; malonic acidemia; and mutations in the AcylCoA Synthetase (ACSF3 ) gene. A typical organic acidemia pattern was observed in five patients, who displayed episodic ketoacidosis with or without hypoglycemia, progressive to coma. Western analysis of fibroblast extracts of five patients showed cross-reacting material. Viral expression of ACSF3 restored function. The ACSF3 gene has been described as an orphan member of the acyl Coenzyme A (CoA) synthetase gene family. This group of enzymes catalyzes the esterification of carboxylic acid substrates to their CoA derivative. The structure of ACSF3 was found to be similar to the malonylCoA synthase of Bradyrhizobium japonicum.
